Paxillin’s LD4 motif interacts with bcl-2.

Publications // Sheibani Lab // Mar 01 2008

PubMed ID: 17786945

Author(s): Sheibani N, Tang Y, Sorenson CM. Paxillin’s LD4 motif interacts with bcl-2. J Cell Physiol. 2008 Mar;214(3):655-61. PMID 17786945

Journal: Journal Of Cellular Physiology, Volume 214, Issue 3, Mar 2008

Bcl-2 is the founding member of a family of proteins which influences cell survival in response to a variety of stimuli including those from growth factor receptors and integrins. However, how these activities are coordinated through bcl-2 requires further investigation. bcl-2 interacts with paxillin, potentially linking cell survival and cell adhesive pathways. Paxillin is an adapter protein implicated in growth factor and integrin-mediated signal transduction pathways. Previous work in this laboratory demonstrated that loss of bcl-2 affects cell adhesion and migration characteristics of renal epithelial cells, perhaps through disruption of its interaction with paxillin. Here studies were performed to determine the bcl-2 binding motif in paxillin. The amino-terminal portion of paxillin, specifically its LD4 motif, was found to associate with bcl-2. However, the amino-terminal portion of paxillin with the LD4 domain deleted did not associate with bcl-2. The corresponding LD motif in other paxillin family members, Hic-5 and leupaxin, did not associate with bcl-2. Mutations in paxillin’s LD4 motif made to mimic Hic-5 and leupaxin LD4-like motifs (E(268) –> R or S(272) –> H) abolished its association with bcl-2. Incubation of embryonic kidneys with paxillin’s LD4 motif disrupted ureteric bud branching and morphogenesis, while incubation with the comparable Hic-5 LD motif did not significantly affect morphogenesis. These data suggest that paxillin’s association with bcl-2 plays a unique role during kidney development that other paxillin family members may not be able to fulfill.

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